Is BRCA2 p.Gln3350Lys (c.10048C>A) pathogenic?

BRCA2 p.Gln3350Lys (c.10048C>A) is classified Uncertain significance in BRCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-30). AlphaMissense: likely benign (0.1956); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with BRCA2 p.Gln3350Lys (c.10048C>A)?

BRCA2 p.Gln3350Lys (c.10048C>A) is associated with hereditary neoplastic syndrome (ClinVar).

How common is BRCA2 p.Gln3350Lys (c.10048C>A) in the general population?

BRCA2 p.Gln3350Lys (c.10048C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BRCA2 p.Gln3350Lys (c.10048C>A)?

AlphaMissense predicts likely benign (score 0.1956) — an in-silico prediction, not a clinical call.

BRCA2 p.Gln3350Lys

c.10048C>A · rs2137666093 · VCV3224978

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1956 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.1956	likely benign
REVEL	0.294	indeterminate
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.31 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.6	GERP 2.3, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 35 kb · p 0.00024 · regional, not allelic
Overall
CADD	26.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BRCA2
Protein: p.Gln3350Lys
Coding: c.10048C>A
MANE Select: NM_000059
dbSNP: rs2137666093
Type: single nucleotide variant
Location: chr13:32398561 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)

Full BRCA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BRCA2 p.Gln3350Arg Uncertain significance ★★ same residue
BRCA2 p.Gln3350His Uncertain significance ★★ same residue
BRCA2 p.Gln3350fs Uncertain significance ★ same residue
BRCA2 p.Gln3350Glu Uncertain significance ★ ⚠ same residue
BRCA2 p.Gln3350Leu Uncertain significance ★ same residue
BRCA2 p.Gln3350Ter Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 c.316+1G>T Pathogenic ★★★ same condition
BRCA2 c.316+2T>C Pathogenic ★★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/brca2-p-gln3350lys (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown